Naphthalene is metabolized by cytochrome P-450 enzymes to two epoxides, namely, (1S), (2R)-naphthalene oxide and (1R), (2S)-- naphthalene oxide. In the presence of glutathione and glutathione transferase mixtures of these epoxides are converted to three glutathione conjugates. Conjugates (1) and (3), which are (1S)- hydroxy-(2S) glutathion-S-yl-1,2,-dihydronaphthalene and (1R)- glutathion-S-yl-(2S)-hydroxy-1,2-dihydronaphthalene are formed solely from (1S), (2R)-naphthalene oxide. Conjugate (2), which is (1R)-hydroxy-(2R)-glutathion-S-yl-1,2-dihydronaphthalene is formed solely from (1R), (2S)-naphthalene oxide (Buckpitt, personal communication). Two isozymes of cytochrome P-450 that metabolize naphthalene have been isolated from mouse liver. End group analyses indicate that they are isozymes not previously isolated. Since reconstituted systems containing cytochrome P-450 and glutathione transferases convert naphthalene almost solely to conjugate 2, cytochrome P-450N must oxidize naphthalene almost solely to (1R), (2S)-naphthaloene oxide. By contrast, systems containing cytochrome P-450S oxidize naphthalene to both epoxides but preferentially to (1S), (2R)-naphthalene oxide. Studies on the metabolism of naphthalene by microsomes of mouse lung suggest that they contain predominantly cytochrome P-450N. Indeed an antibody against cytochrome P-450(N) almost completely blocked the formation of conjugate 2. By contrast studies with microsomes from mouse liver, suggest that they contain both forms, but mainly cytochrome P-450S. Since naphthalene causes pulmonary damage but not liver necrosis in mice, it may be that (1R), (2S)-naphthalene oxide is more toxic than (1S), (2R)-naphthalene oxide.
